US7132512B2 - Medicament for the treatment of chlamydial infection - Google Patents
Medicament for the treatment of chlamydial infection Download PDFInfo
- Publication number
- US7132512B2 US7132512B2 US10/634,914 US63491403A US7132512B2 US 7132512 B2 US7132512 B2 US 7132512B2 US 63491403 A US63491403 A US 63491403A US 7132512 B2 US7132512 B2 US 7132512B2
- Authority
- US
- United States
- Prior art keywords
- protein
- pneumoniae
- kda
- peptide
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related, expires
Links
- 239000003814 drug Substances 0.000 title description 10
- 206010061041 Chlamydial infection Diseases 0.000 title description 3
- 201000000902 chlamydia Diseases 0.000 title description 3
- 208000012538 chlamydia trachomatis infectious disease Diseases 0.000 title description 3
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 27
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 10
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 229920001184 polypeptide Polymers 0.000 claims 2
- 241001647372 Chlamydia pneumoniae Species 0.000 abstract description 32
- 208000015181 infectious disease Diseases 0.000 abstract description 18
- 238000003745 diagnosis Methods 0.000 abstract description 5
- 208000029078 coronary artery disease Diseases 0.000 abstract description 4
- 230000002265 prevention Effects 0.000 abstract description 4
- 201000001320 Atherosclerosis Diseases 0.000 abstract description 3
- 206010003211 Arteriosclerosis coronary artery Diseases 0.000 abstract description 2
- 208000026758 coronary atherosclerosis Diseases 0.000 abstract description 2
- 108090000623 proteins and genes Proteins 0.000 description 45
- 102000004169 proteins and genes Human genes 0.000 description 42
- 239000000427 antigen Substances 0.000 description 21
- 102000036639 antigens Human genes 0.000 description 19
- 108091007433 antigens Proteins 0.000 description 19
- 239000012634 fragment Substances 0.000 description 18
- 230000002163 immunogen Effects 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 12
- 210000002966 serum Anatomy 0.000 description 10
- OBMZMSLWNNWEJA-XNCRXQDQSA-N C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 Chemical compound C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 OBMZMSLWNNWEJA-XNCRXQDQSA-N 0.000 description 8
- 101710176384 Peptide 1 Proteins 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- HEGSGKPQLMEBJL-RKQHYHRCSA-N octyl beta-D-glucopyranoside Chemical compound CCCCCCCCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HEGSGKPQLMEBJL-RKQHYHRCSA-N 0.000 description 8
- 239000000499 gel Substances 0.000 description 7
- 238000003119 immunoblot Methods 0.000 description 7
- 241000283973 Oryctolagus cuniculus Species 0.000 description 6
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 6
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 6
- 150000001413 amino acids Chemical class 0.000 description 6
- 239000011230 binding agent Substances 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 125000003729 nucleotide group Chemical group 0.000 description 6
- 238000012163 sequencing technique Methods 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 102000053642 Catalytic RNA Human genes 0.000 description 5
- 108090000994 Catalytic RNA Proteins 0.000 description 5
- 241000606153 Chlamydia trachomatis Species 0.000 description 5
- 229920001213 Polysorbate 20 Polymers 0.000 description 5
- 206010057190 Respiratory tract infections Diseases 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 239000002773 nucleotide Substances 0.000 description 5
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 5
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 5
- 108091092562 ribozyme Proteins 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 229940021995 DNA vaccine Drugs 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 4
- 108090000190 Thrombin Proteins 0.000 description 4
- 238000009739 binding Methods 0.000 description 4
- 229940098773 bovine serum albumin Drugs 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000013507 mapping Methods 0.000 description 4
- 238000006386 neutralization reaction Methods 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 229960004072 thrombin Drugs 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 241000606161 Chlamydia Species 0.000 description 3
- 108010041986 DNA Vaccines Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000013019 agitation Methods 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 210000003000 inclusion body Anatomy 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 238000004091 panning Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 238000007675 cardiac surgery Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229940038705 chlamydia trachomatis Drugs 0.000 description 2
- NKLPQNGYXWVELD-UHFFFAOYSA-M coomassie brilliant blue Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=C1 NKLPQNGYXWVELD-UHFFFAOYSA-M 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 150000007523 nucleic acids Chemical group 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 238000011533 pre-incubation Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- QRXMUCSWCMTJGU-UHFFFAOYSA-N 5-bromo-4-chloro-3-indolyl phosphate Chemical compound C1=C(Br)C(Cl)=C2C(OP(O)(=O)O)=CNC2=C1 QRXMUCSWCMTJGU-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- 241001647378 Chlamydia psittaci Species 0.000 description 1
- 241000201569 Chlamydophila pneumoniae CWL029 Species 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000672609 Escherichia coli BL21 Species 0.000 description 1
- 208000023661 Haematological disease Diseases 0.000 description 1
- 239000007993 MOPS buffer Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 208000029082 Pelvic Inflammatory Disease Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229940022005 RNA vaccine Drugs 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000000539 amino acid group Chemical class 0.000 description 1
- 230000009830 antibody antigen interaction Effects 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000003182 dose-response assay Methods 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000000521 hyperimmunizing effect Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 229960001438 immunostimulant agent Drugs 0.000 description 1
- 239000003022 immunostimulating agent Substances 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 238000011587 new zealand white rabbit Methods 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- -1 polyethylene Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 235000015096 spirit Nutrition 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/295—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Chlamydiales (O)
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/53—DNA (RNA) vaccination
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
Definitions
- the present invention concerns treatment, prevention and diagnosis of infection due to Chlamydia pneumoniae and in particular to the prevention and treatment of atherosclerosis, including coronary atherosclerosis, caused by same.
- C. pneumoniae is associated with atherosclerosis but no definitive link between the two has yet been established (Hammerschlag, M. R., 1998, Eur. J. Clin. Microbiol. Infect. Dis., 17: 305–308). Friedank, H. M. et al. (1993, Eur. J. Clin. Microbiol. Infect. Dis., 12(12): 947–951) identify a 54 kDa C. pneumoniae antigen which was recognised by 93% of sera positive for C. pneumoniae , the antigen appearing to be located on the surface of elementary bodies. Wiedman, A. A. M. et al. (1997, Clin. Diagn. Labs. Immunol., 4(6):700–704) showed the infectivity of C. pneumoniae elementary bodies to be slightly reduced by the use of antibody specific against a 54 kDa C. pneumoniae protein.
- the present inventor has now succeeded in isolating, purifying and identifying a C. pneumoniae protein which (together with inhibitors of same, such as antibodies) is protective and therapeutic against C. pneumoniae infection.
- the therapeutic role of the protein has previously neither been suggested nor disclosed.
- a C. pneumoniae protein having the amino acid sequence of SEQ ID NO: 2, for use in a method of treatment or diagnosis of the human or animal body.
- the amino acid sequence has been confirmed by N-terminal amino-acid sequencing (see “Experimental” below) and the protein has a theoretical molecular weight of 50.8 kDa, although post-translational modifications such as glycosylation may of course affect its apparent molecular weight as determined by e.g. SDS-PAGE. Experiments (below) have shown it to have an apparent molecular weight of 51 kDa on SDS-PAGE gels.
- nucleotide sequence coding for a protein according to the present invention for use in a method of treatment or diagnosis of the human or animal body.
- Such a nucleotide sequence may have the sequence of SEQ ID NO: 1. Modified nucleotide sequences having codons encoding the same amino acid sequence will be readily apparent to one skilled in the art.
- the nucleotide sequence of the present invention and the amino acid sequence it encodes are already known from the Chlamydia Genome Project ( C. pneumoniae CWL029/CPn0809), as is an apparent C. trachomatis homologue (CT578). However, therapeutic and diagnostic uses for same have not been previously suggested.
- the invention also extends to encompass forms of the protein which have been insubstantially modified (i.e. which have been partially modified), particularly forms of the protein which display the same immunogenic properties as the protein itself.
- partial modification and “partially modified” is meant, with reference to amino acid sequences, a partially modified form of the molecule which retains substantially the properties of the molecule from which it is derived, although it may of course have additional functionality. Partial modification may, for example, be by way of addition, deletion or substitution of amino acid residues. Substitutions may be conserved substitutions.
- the partially modified molecule may be a homologue of the molecules from which it was derived. It may, for example, have at least 70% homology with the molecule from which it was derived. It may for example have at least 80, 90 or 95% homology with the molecule from which it was derived. An example of a homologue is an allelic mutant.
- Also provided according to the present invention is the use of a protein, immunogenic fragment thereof or nucleic acid sequence encoding same according to the present invention in the manufacture of a medicament for the treatment of infection due to C. pneumoniae.
- Immunogenic fragments of the protein include any fragment of the protein which elicits an immune response, and includes epitopes.
- Analogues (mimotopes) of epitopes may be readily created, the mimotopes having different sequences but displaying the same epitope and thus the term “immunogenic fragments” also encompasses immunogenic analogues of the fragments e.g. mimotopes.
- Epitopes may be readily determined and mimotopes readily designed (Geysen, H. M. et al., 1987, Journal of Immunological Methods, 102: 259–274; Geysen, H. M. et al.1988, J. Mol. Recognit., 1(1):32–41; Jung, G.
- Such an immunogenic fragment carrying epitopes may also be described as being a peptide having the amino acid sequence of the immunogenic fragment and which carries an epitope.
- the present inventor has succeeded in isolating a number of epitopes (immunogenic fragments) of the protein of the present invention.
- epitopes having the amino acid sequence of any one of SEQ ID NOs: 4–14.
- SEQ ID NOs: 5–7 provide an overlapping set of highly immunogenic peptides—as can be seen from the experimental data (below)
- SEQ ID NO: 5 provides for especially good results.
- excellent results are also obtained from SEQ ID NO: 8.
- the protein, immunogenic fragments thereof and nucleic acid sequences encoding same may be used in therapy, both prophylactically (e.g. as immunostimulants such as vaccines) and for treatment of infection due to C. pneumoniae .
- a nucleotide sequence encoding the protein or immunogenic fragment thereof may be used in the manufacture of a DNA vaccine (Montgomery, D. L. et al., 1997, Pharmacol. Ther., 74(2): 195–205; Donnelly, J. J. et al., 1997, Annu. Rev. Immunol., 15: 617–648; Manickan, E. et al., 1997, Crit. Rev. Immunol., 17(2): 139–154).
- Binding agents and inhibitors such as antibodies or other neutralising agents
- Binding agents may also be used both diagnostically and therapeutically.
- Binding agents have a target to which they are specific, and in the case of a binding agent being an antibody, the target is an antigen.
- An example of a therapeutic medicament is antibody specific against the protein of the present invention, and this may be employed in immunotherapy, for example passive immunotherapy.
- Antibodies, their manufacture and use are well known (Harlow, E. and Lane, D., “Using Antibodies—A Laboratory Manual”, Cold Spring Harbor Laboratory Press, New York, 1998) and so antibodies and antigen binding fragments thereof will be readily apparent to one skilled in the art, and reference herein to antibodies is also reference to antigen binding fragments unless stated otherwise.
- inhibitors such as ribozymes, antisense oligonucleotides and DNA vaccines will be readily apparent to one skilled in the art (Fries, P. C., 1999, “DNA Vaccines”, New England Journal of medicine, 341: 1623–1624; Leitner, W. W. et al., 1999, “DNA and RNA based vaccines: principles, progress and prospects”, Vaccine, 18: 765–777; Muotri, A. R. et al., 1999, “Ribozymes and the anti-gene therapy: how a catalytic RNA can be used to inhibit gene function”, Gene, 237: 303–310; Rossi, J.
- the present invention also provides the use of a inhibitor specific to the protein of the present invention in the manufacture of a medicament for the treatment of infection due to C. pneumoniae.
- Also provided according to the present invention is a method of manufacture of a medicament for the treatment of infection due to C. pneumoniae , characterised in the use of a protein, immunogenic fragment or inhibitor according to the present invention.
- Also provided according to the present invention is a method of treatment of infection due to C. pneumoniae (e.g. of a patient in need of same), comprising the step of administering to a patient a medicament comprising a protein immunogenic fragment or inhibitor according to the present invention.
- a medicament comprising a protein immunogenic fragment or inhibitor according to the present invention.
- the exact dose of medicament administered to a patient may be readily determined using simple dose-response assays.
- Medicaments may additionally comprise a pharmaceutically acceptable carrier, diluent or excipient (Remington's Pharmaceutical Sciences and US Pharmacopeia, 1984, Mack Publishing Company, Easton, Pa., USA)
- the protein of the present invention is diagnostic for infection due to C. pneumonia .
- Binding agents specific to the protein of the present invention may also be used diagnostically, for example in an ELISA-type test.
- a protein, immunogenic fragment or binding agent according to the present invention in the manufacture of a diagnostic test for C. pneumoniae.
- a diagnostic test method for infection due to C. pneumoniae comprising the steps of:
- test methods may also be performed using other binding agents specific to the protein of the present invention.
- kit of parts for performing such a test characterised in that it comprises antibody specific against the protein of the present invention.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/634,914 US7132512B2 (en) | 1999-02-05 | 2003-08-06 | Medicament for the treatment of chlamydial infection |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9902555.3A GB9902555D0 (en) | 1999-02-05 | 1999-02-05 | Medicament |
| GB9902555.3 | 1999-02-05 | ||
| PCT/GB2000/000237 WO2000046359A2 (en) | 1999-02-05 | 2000-01-28 | Medicament |
| US88931401A | 2001-11-20 | 2001-11-20 | |
| US10/634,914 US7132512B2 (en) | 1999-02-05 | 2003-08-06 | Medicament for the treatment of chlamydial infection |
Related Parent Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/GB2000/000237 Continuation WO2000046359A2 (en) | 1999-02-05 | 2000-01-28 | Medicament |
| US09889314 Continuation | 2000-01-28 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| US20040029806A1 US20040029806A1 (en) | 2004-02-12 |
| US7132512B2 true US7132512B2 (en) | 2006-11-07 |
Family
ID=10847149
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US10/634,914 Expired - Fee Related US7132512B2 (en) | 1999-02-05 | 2003-08-06 | Medicament for the treatment of chlamydial infection |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US7132512B2 (de) |
| EP (1) | EP1149162B1 (de) |
| AT (1) | ATE425248T1 (de) |
| AU (1) | AU2119200A (de) |
| CA (1) | CA2359354C (de) |
| DE (1) | DE60041753D1 (de) |
| GB (1) | GB9902555D0 (de) |
| WO (1) | WO2000046359A2 (de) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU5366099A (en) | 1998-08-20 | 2000-03-14 | Connaught Laboratories Limited | Nucleic acid molecules encoding inclusion membrane protein of (chlamydia) |
| AU5365999A (en) | 1998-08-20 | 2000-03-14 | Connaught Laboratories Limited | Nucleic acid molecules encoding pomp91a protein of (chlamydia) |
| US6686339B1 (en) | 1998-08-20 | 2004-02-03 | Aventis Pasteur Limited | Nucleic acid molecules encoding inclusion membrane protein C of Chlamydia |
| US6649370B1 (en) | 1998-10-28 | 2003-11-18 | Aventis Pasteur Limited | Chlamydia antigens and corresponding DNA fragments and uses thereof |
| US6607730B1 (en) | 1998-11-02 | 2003-08-19 | Aventis Pasteur Limited/Aventis Pasteur Limitee | Chlamydia antigens and corresponding DNA fragments and uses thereof |
| JP2002531093A (ja) | 1998-12-01 | 2002-09-24 | アベンティス、パストゥール、リミテッド | クラミジア抗原および対応するｄｎａ断片ならびにその使用 |
| WO2000034483A2 (en) | 1998-12-08 | 2000-06-15 | Corixa Corporation | Compounds and methods for treatment and diagnosis of chlamydial infection |
| US20020061848A1 (en) | 2000-07-20 | 2002-05-23 | Ajay Bhatia | Compounds and methods for treatment and diagnosis of chlamydial infection |
| GB9828000D0 (en) | 1998-12-18 | 1999-02-10 | Chiron Spa | Antigens |
| US7297341B1 (en) | 1998-12-23 | 2007-11-20 | Sanofi Pasteur Limited | Chlamydia antigens and corresponding DNA fragments and uses thereof |
| US6808713B1 (en) | 1998-12-28 | 2004-10-26 | Aventis Pasteur Limited | Chlamydia antigens and corresponding DNA fragments and uses thereof |
| CA2356057A1 (en) | 1998-12-28 | 2000-07-06 | Aventis Pasteur Limited | Chlamydia antigens and corresponding dna fragments and uses thereof |
| GB9902555D0 (en) | 1999-02-05 | 1999-03-24 | Neutec Pharma Plc | Medicament |
| MXPA01009256A (es) | 1999-03-12 | 2003-07-14 | Aventis Pasteur | Antigenos de chlamydia y fragmentos de acido desoxirribonucleico correspondientes y usos de los mismos. |
| WO2000066739A2 (en) | 1999-05-03 | 2000-11-09 | Aventis Pasteur Limited | Chlamydia antigens and corresponding dna fragments and uses thereof |
| ATE384793T1 (de) | 1999-09-20 | 2008-02-15 | Aventis Pasteur | Chlamydia antigene und entsprechende dna- fragmente und ihre verwendungen |
| US6632663B1 (en) | 1999-09-22 | 2003-10-14 | Aventis Pasteur Limited | DNA immunization against chlamydia infection |
| CA2395499C (en) | 1999-12-22 | 2011-10-25 | Aventis Pasteur Limited | Chlamydia antigens and corresponding dna fragments and uses thereof |
| DE60133190T2 (de) | 2000-04-21 | 2009-04-02 | CORIXA CORP., Wilmington | Verbindungen und verfahren zur behandlung und diagnose von chlamydia-infektionen |
| CA2408199A1 (en) | 2000-05-08 | 2001-11-15 | Aventis Pasteur Limited | Chlamydia antigens and corresponding dna fragments and uses thereof |
| WO2002002606A2 (en) | 2000-07-03 | 2002-01-10 | Chiron S.P.A. | Immunisation against chlamydia pneumoniae |
| WO2002095413A2 (en) * | 2001-05-23 | 2002-11-28 | The University Of British Columbia | Diagnosis of vascular disease susceptibility using bacteriophage phi-cpn1 host chlamydia |
| DE102006003814A1 (de) * | 2006-01-26 | 2007-08-02 | Sirs-Lab Gmbh | Verfahren zur in-vitro-Diagnose von Chlamydophila pneumoniae Infektionen |
| JP2012519482A (ja) | 2009-03-06 | 2012-08-30 | ノバルティス アーゲー | クラミジア抗原 |
| KR101297037B1 (ko) * | 2010-03-26 | 2013-08-14 | 숙명여자대학교산학협력단 | 혈관신생촉진용 펩타이드 및 이의 용도 |
| KR101335203B1 (ko) * | 2010-03-26 | 2013-11-29 | 숙명여자대학교산학협력단 | 혈관신생촉진용 펩타이드 및 이의 용도 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996009320A1 (en) | 1994-09-20 | 1996-03-28 | Hitachi Chemical Company, Ltd. | Antigenic polypeptide of chlamydia pneumoniae |
| WO1999027105A2 (en) | 1997-11-21 | 1999-06-03 | Genset | Chlamydia pneumoniae genomic sequence and polypeptides, fragments thereof and uses thereof, in particular for the diagnosis, prevention and treatment of infection |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999028475A2 (en) | 1997-11-28 | 1999-06-10 | Genset | Chlamydia trachomatis genomic sequence and polypeptides, fragments thereof and uses thereof, in particular for the diagnosis, prevention and treatment of infection |
| EP1133572A4 (de) | 1998-11-12 | 2005-06-15 | Univ California | Genomsequenz von chlamydia pneumoniae |
| US20020061848A1 (en) | 2000-07-20 | 2002-05-23 | Ajay Bhatia | Compounds and methods for treatment and diagnosis of chlamydial infection |
| WO2000034483A2 (en) | 1998-12-08 | 2000-06-15 | Corixa Corporation | Compounds and methods for treatment and diagnosis of chlamydial infection |
| US6565856B1 (en) | 1998-12-08 | 2003-05-20 | Corixa Corporation | Compounds and methods for treatment and diagnosis of chlamydial infection |
| GB9828000D0 (en) | 1998-12-18 | 1999-02-10 | Chiron Spa | Antigens |
| GB9902555D0 (en) | 1999-02-05 | 1999-03-24 | Neutec Pharma Plc | Medicament |
| WO2000066739A2 (en) | 1999-05-03 | 2000-11-09 | Aventis Pasteur Limited | Chlamydia antigens and corresponding dna fragments and uses thereof |
| ATE384793T1 (de) | 1999-09-20 | 2008-02-15 | Aventis Pasteur | Chlamydia antigene und entsprechende dna- fragmente und ihre verwendungen |
| US6632663B1 (en) | 1999-09-22 | 2003-10-14 | Aventis Pasteur Limited | DNA immunization against chlamydia infection |
| CA2395499C (en) | 1999-12-22 | 2011-10-25 | Aventis Pasteur Limited | Chlamydia antigens and corresponding dna fragments and uses thereof |
| DE60133190T2 (de) | 2000-04-21 | 2009-04-02 | CORIXA CORP., Wilmington | Verbindungen und verfahren zur behandlung und diagnose von chlamydia-infektionen |
| CA2408199A1 (en) | 2000-05-08 | 2001-11-15 | Aventis Pasteur Limited | Chlamydia antigens and corresponding dna fragments and uses thereof |
| WO2002002606A2 (en) | 2000-07-03 | 2002-01-10 | Chiron S.P.A. | Immunisation against chlamydia pneumoniae |
-
1999
- 1999-02-05 GB GBGB9902555.3A patent/GB9902555D0/en not_active Ceased
-
2000
- 2000-01-28 DE DE60041753T patent/DE60041753D1/de not_active Expired - Lifetime
- 2000-01-28 WO PCT/GB2000/000237 patent/WO2000046359A2/en active Application Filing
- 2000-01-28 EP EP00901235A patent/EP1149162B1/de not_active Expired - Lifetime
- 2000-01-28 AT AT00901235T patent/ATE425248T1/de not_active IP Right Cessation
- 2000-01-28 AU AU21192/00A patent/AU2119200A/en not_active Abandoned
- 2000-01-28 CA CA002359354A patent/CA2359354C/en not_active Expired - Fee Related
-
2003
- 2003-08-06 US US10/634,914 patent/US7132512B2/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996009320A1 (en) | 1994-09-20 | 1996-03-28 | Hitachi Chemical Company, Ltd. | Antigenic polypeptide of chlamydia pneumoniae |
| EP0784059A1 (de) | 1994-09-20 | 1997-07-16 | Hitachi Chemical Co., Ltd. | Antigenes polypeptid aus chlamydia pneumoniae |
| US6165478A (en) * | 1994-09-20 | 2000-12-26 | Hitachi Chemical Company, Ltd. | DNA encoding Chlamydia pneumoniae antigenic polypeptide |
| WO1999027105A2 (en) | 1997-11-21 | 1999-06-03 | Genset | Chlamydia pneumoniae genomic sequence and polypeptides, fragments thereof and uses thereof, in particular for the diagnosis, prevention and treatment of infection |
Non-Patent Citations (6)
| Title |
|---|
| Accession No. AAR94585, AAR94579, AAR94586 or AAWO 1743. * |
| Iijima et al. "Characterization of Chlamydia pneumoniae species-specific proteins immunodominant in humans" Journal of Clinical Microbiology, 32:3 (Mar. 1994) pp. 583-588 (XP002115816). |
| Kalman et al. "Comparative genomes of Chlamydia pneumoniae and C. trachomatis " Nature Genetics. vol. 21 (Apr. 1999) pp. 385-389 (XP002141432). |
| Kanamoto et al. "Antigenic characterization of Chlamydia pneumoniae isolated in Hiroshima, Japan" Microbiology and Immunology, 37:6 (Jan. 1993) pp. 495-498 (XP002088968). |
| Kornak et al. "Sequence analysis of the gene encoding the Chlamydia pneumoniae Dnak protein homolog" Infection and Immunity, US, American Society for Microbiology 59:2 (1991) pp. 721-725 (XP002076846). |
| Perez Melgosa et al. "Isolation and characterization of a gene encoding a Chlamydia pneumoniae 76-kilodalton protein containing a species-specific epitope" Infection and Immunity, 62:3 (1994) pp. 880-886 (XP002076845). |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2000046359A3 (en) | 2000-12-07 |
| US20040029806A1 (en) | 2004-02-12 |
| EP1149162A2 (de) | 2001-10-31 |
| GB9902555D0 (en) | 1999-03-24 |
| CA2359354C (en) | 2008-07-08 |
| CA2359354A1 (en) | 2000-08-10 |
| EP1149162B1 (de) | 2009-03-11 |
| WO2000046359A2 (en) | 2000-08-10 |
| ATE425248T1 (de) | 2009-03-15 |
| AU2119200A (en) | 2000-08-25 |
| DE60041753D1 (de) | 2009-04-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7132512B2 (en) | Medicament for the treatment of chlamydial infection | |
| JP2665332B2 (ja) | ヘルペス・シンプレツクスウイルスのワクチン接種の材料および方法 | |
| US7179448B2 (en) | Recombinant constructs of Borrelia burgdorferi | |
| US20030235818A1 (en) | Immunogenic peptides, and method of identifying same | |
| JP2003529319A (ja) | ＨＩＶ−１ｇｐ４１を標的化する広範に中和する抗体を誘発する方法 | |
| CA2585011A1 (en) | Chlamydia trachomatis antigens for vaccine and diagnostic use | |
| US6174528B1 (en) | Synthetic peptides and vaccines comprising same | |
| WO2022003119A1 (en) | Cross-reactive coronavirus vaccine | |
| Su et al. | Immunogenicity of a synthetic oligopeptide corresponding to antigenically common T-helper and B-cell neutralizing epitopes of the major outer membrane protein of Chlamydia trachomatis | |
| Shanafelt et al. | Epitopes on the outer surface protein A of Borrelia burgdorferi recognized by antibodies and T cells of patients with Lyme disease. | |
| CA2228522A1 (en) | Hybrid protein comprising t-helper cell stimulating epitopes and b-cell epitopes from the major outer membrane protein of chlamydia trachomatis and its use as a vaccine | |
| US6838085B2 (en) | DNA immunization against Chlamydia infection | |
| EP1141305B1 (de) | Chimärisches gen, dass für die antigenischen determinanten von vier protein aus l. infantum kodiert | |
| JP4717213B2 (ja) | 新規なアミノ酸配列、そのアミノ酸配列をコードするｄｎａ、かかる配列に向けられた抗体およびその種々の使用 | |
| AU772015B2 (en) | Peptide fragments of cholera toxin B or enterotoxin B as vaccine adjuvants | |
| SURI et al. | Evaluation of recombinant protein r140, a polypeptide segment of tegumental glycoprotein Sm25, as a defined antigen vaccine against Schistosoma mansoni | |
| Ivanyi et al. | Predominant recognition of species‐specific determinants of the GroES homologues from Mycobacterium leprae and M. tuberculosis | |
| US6689364B2 (en) | Borrelia burgdorferi polypeptides and uses thereof | |
| WO2006009862A2 (en) | Amebiasis subunit vaccine | |
| WO2004014945A1 (en) | Gp41 epitope and uses thereof for the treatment of hiv infections |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AS | Assignment |
Owner name: NEUTEC PHARMA PLC, GREAT BRITAIN Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BURNIE, JAMES PETER;MATTHEWS, RUTH CHRISTINE;REEL/FRAME:014377/0320 Effective date: 20010711 |
|
| AS | Assignment |
Owner name: NEUTEC PHARMA LIMITED, UNITED KINGDOM Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:NEU TEC PHARMA PLC;REEL/FRAME:021138/0778 Effective date: 20080128 |
|
| FPAY | Fee payment |
Year of fee payment: 4 |
|
| REMI | Maintenance fee reminder mailed | ||
| LAPS | Lapse for failure to pay maintenance fees | ||
| STCH | Information on status: patent discontinuation |
Free format text: PATENT EXPIRED DUE TO NONPAYMENT OF MAINTENANCE FEES UNDER 37 CFR 1.362 |
|
| FP | Lapsed due to failure to pay maintenance fee |
Effective date: 20141107 |